Failed Drugs, Fizzling Vaccines and Faith

When orthodox medicine and its great professors abandon you to the most horrible death; when all scientific pundits with their Nobel Prizes let themselves be flouted by a miserable virus despite their phenomenal research budgets, how can you fail to go after the last glimmer of hope no matter where, in hell if necessary: Josef Stein

This pandemic has brought to attention how unprepared we really are. Advancement in science and leaps in technology had instilled a sense of invincibility among us. The templates we devised for the containment of emergent diseases appear fallible, while the scientific community is puzzled by this novel virus.

Science is repurposing old and fossilised drugs. Vaccines and biologicals long abandoned are suddenly being infused with a fresh lease of life. Repackaging and revival of ineffective therapies and toxic compounds reiterate our desperation. It almost seems as if our arsenal against SARS CoV-2 is redundant and antiquated.

TRINITY OF LETHAL VIRUSES

Vaccine science is a complex area. There is no effective vaccine against SARS-2003, and MERS-2012. Both the diseases are caused by viruses similar to SARS CoV-2, which causes COVID-19. The corollary is if there was a SARS CoV-1 vaccine, it could have been rapidly deployed for COVID-19. It is highly plausible that such a vaccine could have at least afforded partial immunity against SARS CoV-2. The reason for not developing a SARS-2003 or MERS-2012 vaccine is partially profit factors (both were not pandemics, only very small numbers were infected) and technical difficulties. It underlines two things — first, it was a missed opportunity, and second, developing an effective vaccine against SARS viruses could be a daunting process.

NOXIOUS QUININE: THE JESUIT’S BARK

One of the first drugs to appear in the fight against COVID-19 was the old anti-malarial hydroxychloroquine (a derivative of Quinine or Jesuit's Bark — from a Peruvian tree). Once hailed as effective against malaria, it has lost its ground due to resistance from the parasite. Further, hydroxychloroquine has serious cardiac side-effects; it has caused fatalities in otherwise healthy individuals who consumed it to fight the COVID-19. The sine qua non of medical practice is to first ‘do no harm’. But in the curious case of hydroxychloroquine, the prevention and treatment seem to be worse than the disease.

DISEASE-HOPPING ORPHAN ANTIVIRALS

Remdesivir has been touted as an antiviral which could especially target viral multiplication. A failed drug in Ebola virus disease and Lassa virus infection, it was repurposed for the management of COVID-19. The drug did not make the mark in early trials, although a minimal reduction in the number of days to recovery was observed. Favipiravir, another flu drug, which partially worked in pandemic flu, is being tried for COVID-19. These are drugs which were developed for some other disease and redirected to COVID-19. This kind of disease-hopping orphan antivirals dominate the COVID-19 scene.

RECYCLED CANCER DRUGS

There is a sudden surge of interest in anticancer drugs, particularly monoclonal antibodies such as Tocilizumab and its analogues, to target the cytokine storm or increased cytokine levels, a major reason for fatality in COVID-19.

The second approach is to use the convalescent plasma of a person who has recovered from COVID-19. The convalescent plasma contains antibodies from the donor, which can help a victim recover. However, the high cost-factor makes it difficult to implement for a large population.

HOPE QUENCHED

A lot of hope was generated when Oxford's Jenner Institute's team leaders projected an 80% success rate for their Chimp Adeno Viral vector-based vaccine against COVID-19. Disappointingly, the primate study did not yield protection against the aerosol challenge. Had it been successful, it would have been the first effective COVID-19 vaccine from a university of global repute. The vaccine design was based on a failed Ebola vaccine model that was safe, but did not qualify to enter the commercialisation phase. Recent reports indicate that the vaccine is still being worked upon with some success being predicted.

Proponents of the BCG and polio vaccines also received wide publicity. BCG is a bacterial vaccine, which could only partially protect against tuberculosis. While the polio vaccine is a success against polio, the poliovirus is unrelated to the SARS CoV-2 virus. Both these vaccines are being phased out as polio is on its endgame and resurgence of tuberculosis has led to the development of BCG-II.

UNHEARD IMMUNITY

Herd immunity is an interesting lecture topic at schools of medicine and science, but executing such a concept can have unforeseen consequences. If 70% of the population becomes immune against a disease, it is likely the remaining 30% will be protected. However, there are two routes to it. One is allowing 70% people to acquire the infection naturally and become immune to it. The second approach is to use a vaccine to obtain the same endpoints. In both these approaches, allowing the natural infection route can be devastating in a disease like COVID-19. This was a strategic mistake the U.K. made in the beginning of the pandemic, and had to regress their policies later. Similarly, proponents of innate immunity believe in bolstering it. Unfortunately, without immune memory, the protection cannot be longstanding. Immunity is the final frontier between life and death. Tweaking it should be done judiciously.

SPANISH FLU 1918 AND COVID-2019

It is over one hundred years since the Spanish Flu pandemic of 1918, caused by a similar pathogen that had similar transmission dynamics and resulted in approximately 500 million infections and 50 million deaths (these figures could very well be an underestimate). In 2020, are we in no better a position? Has science and medicine really progressed in these hundred years? Are we treading on a false sense of security? With all our advances, are we not expected to fare better? The pandemic of 1918 died a natural death without much intervention. Are we expecting a similar end?

OLD PUBLIC HEALTH STANDS

In the absence of a drug or a vaccine, public health methods are the last resort to save us. Simple, effective, and universally applicable, these methods were quickly deployed the world over. They have yielded benefits. Lockdowns, isolation, quarantine, social-distancing, risk avoidance, prevention of public gatherings — all have proven effective when strictly adhered to. However, due to its implications on the global economy and human mobility, they cannot be indefinitely observed.

References
La Pierre, Dominique 1990, Beyond Love, New York: Warner Books.

Author: Synergia Foundation Research Team